Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

In recent years,with the development of gene testing and new drug research,the diagnosis and treatment of inherited diseases have made rapid progress,corresponding to higher requirements for genetics education.As a teacher of medical genetics,the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a"case-based learning"supported by flipped classroom in order to optimize teaching effects and learning outcomes.The result of this remodeling project proposes a new strategy to guide perspectives course de-sign in future.

Objective:To measure the magnetic field correction factor of reference ionization chamber in a 1.5 T magnetic field and to explore the response of the ionization chamber among different angles between magnetic field and ionization chamber axis.Methods:A home-made magnetic compatible one-dimensional water tank was used to measure the response of PTW30013 and IBA FC65-G in 7 MV photon beam of Elekta Unity with and without magnetic field. The ionizing current was collected by PTW UNIDOS Tango electrometer. The effective measurement point of ionization chamber was positioned to the isocenter of MR-linac using electronic portal image device. The influence on water absorbed dose of reference point was obtained by Monte Carlo calculations.Results:The response of ionization chambers in strong magnetic field was related to the angle between chamber axis and magnetic field. The response of ionization chamber was significantly affected in perpendicular magnetic field with a deviation up to 4.54% compared to parallel magnetic field. The deviation between the magnetic field correction factors measured for parallel or reverse-parallel was 0.03%-0.24%. The magnetic field correction factors for PTW30013 and FC65-G measured in parallel magnetic field were 0.9934±0.0077 and 0.9990±0.0076, respectively.Conclusions:This study experimentally verifies that positioning the ionization chamber axis parallel to the magnetic field direction in MR-linac reference dosimetry can minimize the magnetic field impact. The determined magnetic field correction factor and uncertainty in 1.5 T magnetic field can provide necessary data for establishing an MR-linac reference dosimetry protocol.

Objective To predict the constitutive parameters of a superelastic model of plantar soft tissues based on random forest(RF)and backpropagation(BP)neural network algorithms to improve the efficiency and accuracy of the method for obtaining constitutive parameters.Methods First,a finite element model for a spherical indentation experiment of plantar soft tissues was established,and the spherical indentation experiment process was simulated to obtain a dataset of nonlinear displacement and indentation force,divided into training and testing sets.The established RF and BP neural network(BPNN)models were trained separately.The constitutive parameters of plantar soft tissues were predicted using experimental data.Finally,the mean square error(MSE)and coefficient of determination(R2)were introduced to evaluate the accuracy of the model prediction,and the effectiveness of the model was verified by comparison with the experimental curves.Results Combining the RF and BPNN models with finite element simulation was an effective and accurate method for determining the superelastic constitutive parameters of plantar soft tissues.After training,the MSE of the RF model reached 1.370 2×10-3,and R2 was 0.982 9,whereas the MSE of the BPNN model reached 4.858 1×10-5,and R2 was 0.999 3.The inverse-determined constitutive parameters of the plantar soft tissues suitable for simulation were obtained.The calculated response curves for the two predicted sets of constitutive parameters were in good agreement with the experimental curves.Conclusions The prediction accuracy for the superelastic constitutive parameters of plantar soft tissues based on an artificial intelligence algorithm model is high,and the relevant research results can be applied to study other mechanical properties of plantar soft tissues.This study provides a new method for obtaining the constitutive parameters of plantar soft tissues and helps to quickly diagnose clinical problems,such as plantar soft tissue lesions.

【Objective】 To explore the correlation between the severity of jaundice in ABO hemolytic disease of fetus and newborn (HDFN) and multiple indicators, in order to achieve accurate diagnosis, timely treatment, and prevent complications in ABO HDFN. 【Methods】 From March 2020 to February 2023, a total of 283 ABO HDFN in our hospital were classified into mild, moderate and severe groups based on total bilirubin levels. The differences in basic data, relevant laboratory indicators and the agglutination intensity of the three hemolysis tests were analyzed and compared. 【Results】 In the severe group, 75% (12/16) were male infants, which was significantly higher compared to 37.5% (57/152) in the moderate group (P<0.05). The values (mg/dL) of transcutaneous jaundice in the mild, moderate and severe groups were:forehead 9.88±1.93 vs 12.34±2.01 vs 15.56±2.69, face 10.25±2.27 vs 13.28±2.32 vs 15.99±2.86, chest 9.67±2.16 vs 12.51±2.11 vs 15.33±2.36, respectively. The values(µmol/L) of direct bilirubin (DBIL) and indirect bilirubin (IBIL) were 9.87±2.06 vs 11.90±2.59 vs 16.12±4.73, and 159.36±37.55 vs 252.98±30.52 vs 353.76±55.68, respectively, and the differences between the mild, moderate and severe groups were statistically significant (all P<0.05) . The creatine kinase (CK) values(unit/L) of mild, moderate and severe groups were 664.15±498.26 vs 500.51 ±451.63 vs 402.63±224.27, and the difference between the mild group and the other two groups was statistically significant (P<0.05) . There was no statistically significant difference in the agglutination intensity of the three hemolysis tests among HDFN with different severity of jaundice. 【Conclusion】 Clinicians can predict the severity of jaundice in light of gender, transcutaneous jaundice, DBIL, IBIL and CK of ABO HDFN, for further and graded treatment, so as to avoid the sequelae or even life-threatening consequences caused by ABO HDFN.

Objective:To study the influence of intensive magnet fields on radiation dose measurement, and to demonstrate the feasibility of measuring magnet field correction factor by a combination of medical linac with variable magnet fields in view of needing for accurate measurement of the doses from reference beam arising in MR image-guided radiotherapy.Methods:A photon radiation field and a variable field with 6 MV nominal high voltage were produced by using conventional medical electron linear accelerator equipped with a pair of electromagnets with magnetic field strength up to 1.5 T. Both PTW30013 and PTW31010 ionization chambers were used to test the responses of ionization chambers under different magnetic field strengths at four orientations in which the angles between ionization chamber axis and magnetic field direction were 0°, 180°, 90° and 270°, respectively. The magnetic factors, kB, M was calculated and compared with the reported values in literature. Results:The response of ionization chamber was proportional to the magnetic field strength before it reached to a peak around 1 T, and then fell down as the magnetic field continued to rise. When the magnetic field was 0.35 T, the magnetic factors of PTW31010 were 0.988 2±0.000 3 and 0.997 4±0.000 4 corresponding to 90° and 0° directions, the discrepancy between 0° scenario and literature was 0.05% ± 0.04%. When the magnetic field reached 1.5 T, the magnetic factor of PTW30013 was 0.958 9±0.000 5 at the situation of 90°, which was 0.60% ± 0.05% different from the literature value.Conclusions:Conventional 6 MV medical accelerator equipped with electromagnet can be used to measure the magnetic field factor of reference dosimetry for MRIgRT.

Metastatic triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Combination of systemic chemotherapy and immune checkpoint blockade is effective but of limited benefit due to insufficient intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and the accumulation of immunosuppressive cells. Herein, we designed a lenvatinib- and vadimezan-loaded synthetic high-density lipoprotein (LV-sHDL) for combinational immunochemotherapy of metastatic TNBC. The LV-sHDL targeted scavenger receptor class B type 1-overexpressing 4T1 cells in the tumor after intravenous injection. The multitargeted tyrosine kinase inhibitor (TKI) lenvatinib induced immunogenic cell death of the cancer cells, and the stimulator of interferon genes (STING) agonist vadimezan triggered local inflammation to facilitate dendritic cell maturation and antitumor macrophage differentiation, which synergistically improved the intratumoral infiltration of total and active CTLs by 33- and 13-fold, respectively. LV-sHDL inhibited the growth of orthotopic 4T1 tumors, reduced pulmonary metastasis, and prolonged the survival of animals. The efficacy could be further improved when LV-sHDL was used in combination with antibody against programmed cell death ligand 1. This study highlights the combination use of multitargeted TKI and STING agonist a promising treatment for metastatic TNBC.

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with split hand/foot malformation (SHFM). METHODS: Genomic DNA of the proband and other affected members was extracted from peripheral blood samples. Chromosomal microarray analysis was employed to detect genome-wide copy number variations (CNVs). RESULTS: A 400 kb microduplication was identified in the 10q24.31-q24.32 region among all affected individuals. The microduplication has involved four genes, namely LBX1, BTRC, POLL and DPCD, in addition with part of FBXW4 gene. CONCLUSION The 10q24.31-q24.32 microduplication has segregated with the disease phenotype in this pedigree and probably underlay the SHFM malformation in the patients.
Asian Continental Ancestry Group ; Chromosome Duplication ; Chromosomes, Human, Pair 10 ; genetics ; DNA Copy Number Variations ; Foot Deformities, Congenital ; genetics ; Genetic Testing ; Hand Deformities, Congenital ; genetics ; Humans ; Limb Deformities, Congenital ; genetics ; Pedigree

Solar energy, which is essential for the origin and evolution of all life forms on Earth, can be objectively recorded through attributes such as climatic ambient temperature (CAT), ultraviolet radiation (UVR), and sunlight duration (SD). These attributes have specific geographical variations and may cause different adaptation traits. However, the adaptation profile of each attribute and the selective role of solar energy as a whole during human evolution remain elusive. Here, we performed a genome-wide adaptation study with respect to CAT, UVR, and SD using the Human Genome Diversity Project-Centre Etude Polymorphism Humain (HGDP-CEPH) panel data. We singled out CAT as the most important driving force with the highest number of adaptive loci (6 SNPs at the genome-wide 1 × 10-7 level;401 at the suggestive 1 × 10-5 level). Five of the six genome-wide significant adaptation SNPs were successfully replicated in an independent Chinese population (N = 1395). The corresponding 316 CAT adaptation genes were mostly involved in development and immunity. In addition, 265 (84％) genes were related to at least one genome-wide associationstudy (GWAS)-mapped human trait, being significantly enriched in anthropometric loci such as those associated with body mass index (x2;P<0.005), immunity, metabolic syndrome, and cancer (x2;P<0.05). For these adaptive SNPs, balancing selection was evident in Euro-Asians, whereas obvious positive and/or purifying selection was observed in Africans. Taken together, our study indicates that CAT is the most important attribute of solar energy that has driven genetic adaptation in development and immunity among global human populations. It also supports the non-neutral hypothesis for the origin of disease-predisposition alleles in common diseases.

Objective: To investigate the joint effect of abdominal obesity in childhood and adulthood on adult hypertension. Methods: Based on the data from the China Health and Nutrition Survey (CHNS, 1993-2011), a total of 1 431 subjects who were investigated in both childhood (6 to17 years old) and young adulthood (18 to 35 years old) were selected for the analysis. According to waist circumference (WC) status (normal WC or abdominal obesity) in childhood and adulthood, all subjects were categorized into 4 groups. The multinomial logistic regression model was used to analyze the joint effect of abdominal obesity in childhood and adulthood on adult hypertension and pre-hypertension. Results: Compared to the subjects (n=1 057) who had normal WC in both childhood and adulthood, subjects with abdominal obesity in childhood but with normal WC (n=45) in adulthood didn′t have significantly increased risk of hypertension (OR=1.52, 95%CI: 0.19-12.06). In contrast, those who had normal WC in childhood and abdominal obesity in adulthood (n=289) had increased risk of hypertension (OR=6.48, 95%CI: 3.60-11.66). In addition, subjects with persistent abdominal obesity from childhood to adulthood (n=40) had the highest risk of hypertension (OR=15.98, 95%CI: 5.39-47.35). There was a similar trend for the association of abdominal obesity in childhood and adulthood with adult pre-hypertension, with the corresponding OR (95%CI) of 1.28 (0.66-2.49), 2.90 (2.17-3.89) and 3.49 (1.65-7.40), respectively. Conclusion The joint effect of abdominal obesity in childhood and adulthood increased the risk of adult hypertension and pre-hypertension. There was no statistical significance for subjects who had abdominal obesity in childhood but had normal WC in adulthood when compared to those with normal WC in both childhood and adulthood.